The distinction between protocol deviations and violations reflects the spectrum of severity and impact that departures from protocol requirements may have on trial conduct. All violations are deviations, but not all deviations rise to the level of violations. Understanding this distinction is essential for appropriate categorization, reporting, and corrective action, as regulatory authorities and ethics committees have different expectations for how various categories of non-compliance should be managed and reported.

Protocol deviations encompass any departure from the approved protocol, regardless of cause or impact. Minor deviations, such as a visit occurring slightly outside the protocol-specified window due to scheduling constraints, may have minimal impact on data quality or participant welfare. Major deviations represent more significant departures that may affect data interpretability or participant safety. Protocol violations represent the most serious category, involving departures that significantly impact participant rights, safety, or welfare, or that substantially affect the integrity, accuracy, or reliability of study data.

Classification systems vary across sponsors, institutions, and regulatory jurisdictions, but common factors considered in categorization include impact on participant safety, effect on data quality or interpretability, whether the deviation was intentional or inadvertent, and whether it represents a pattern of non-compliance. Important and major deviations typically require expedited reporting to the IRB/IEC and sponsor. Recurrent deviations at a site may indicate systemic issues requiring intensive intervention or, in serious cases, termination of the site's participation in the trial.